In recent years technologies directed to sensing presence of particles in a channel have made significant advances. One such technology is a Coulter counter, designed and developed by Wallace H Coulter in 1947. The Coulter counter is used for counting and sizing particles and cells. The theory behind a Coulter counter is that there is a change in electrical conductance of an electrically conducting liquid flowing through the channel when a small non-conducting particle passes through the channel. Cells can be modeled as spheres with a non-conducting outer shell, i.e., the cell membrane. As will be discussed below, the coulter counter can detect cells in the channel, thereby allowing the cells to be identified and counted.
The Coulter counter operates by measuring the electrical resistance of a channel. When the channel is dry, the electrical resistance is high, i.e., an open circuit. When an electrically conducting liquid fills the channel, the electrical resistance drops significantly. However, when a cell, with a non-conducting outer membrane, passes through the channel that is filled with the conducting liquid, the cell displaces the liquid. The displacement of the conducting liquid with the cell having a non-conducting membrane results in an increase in the resistance of the channel. The increase in the resistance can be correlated to the size of the cells and the number of the cells.
Today, the Coulter counter is the core of many laboratory equipment used in hospital laboratories. For example, a complete blood count testing machine is used for counting the cells and determining the size of other particles present in a blood sample in an automated manner. The complete blood count testing machine can provide its results in minutes. The function of the complete blood count testing was traditionally performed manually by laboratory technicians. The manual process involved preparing a blood cell stain and manually counting each type of cell under a microscope. This type of manual counting is time consuming and prone to variation from technician to technician.
While Coulter counters have replaced manual counting of blood cell constituents, counters capable of effectively counting smaller nano-sized particles, i.e., particles with sizes in the nano-meter range, i.e., 10−9 m, are only now becoming available. Many of these new systems use expensive and sophisticated equipment. For example, a line of nano-size particle identification technologies are based on imaging light that scatters from the particles. The light scattering technology may use an electron multiplication charge coupled device camera system for improving sensitivity. In addition to expense, these systems have limited capabilities. In particular, the lower limit for particle size may be 10 nm.
In addition to counting nano-sized particles, recent developments in Deoxyribonucleic acid molecule (DNA) sequencing and Ribonucleic acid molecule (RNA) sequencing have generated a need for manipulating DNA and RNA molecules. The DNA and RNA molecules are made of strands with feature sizes as small as 1-2 nm. As a result, a DNA/RNA molecule manipulator must be sensitive to the single-digit nm sized features of the DNA/RNA strands.
Therefore, there is a need for both a counter that can count single nano-meter sized particles and further control and manipulate these particles.